Clinical Significance of Heterozygosity for Mutations of the SLC12A3 Gene Coding for the Thiazide Sensitive Na-Cl Cotransporter

Not Applicable

Completed

• Conditions: Heterozygous Carriers of Gitelman Syndrome

• Registration Number: NCT02035046
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Gitelman syndrome is a salt wasting tubulopathy caused by mutations in the SLC12A3 gene coding for the thiazide sensitive sodium chloride cotransporter. This disease mimics the chronic treatment with thiazide diuretics and is characterized by renal hypokalemia, low to normal blood pressure, hypocalciuria and hypomagnesemia. The purpose of this study is to determine whether the heterozygous carriers present the metabolic risks and/or the benefits of this disease.

Detailed Description

Gitelman syndrome (GS), is an autosomal recessive salt wasting tubulopathy caused mainly by loss of function mutations in the SLC12A3 gene coding for the thiazide sensitive sodium-chloride cotransporter (NCC). Thus, GS mimics a chronic treatment with high doses of thiazide diuretics. NCC is expressed in the distal convoluted tubule, which is responsible for 7% of NaCl reabsorption. GS is the more frequent hereditary tubulopathie with estimated prevalence of 1/40000, which implicates that 1% of general population are heterozygous carriers (600 000 in France). Previous publications suggest that the apparently asymptomatic heterozygous carriers could present some clinical traits of GS or chronic thiazide treatment. These including: beneficial aspects (low blood pressure, low urinary calcium excretions) or metabolic risks (hypokalemia, insulin resistance). Nevertheless, these studies do not evaluate all the aspects and blood pressure was evaluated once in hospital setting. This study aims to compare home monitoring blood pressure; salt balance; potassium, glucose lipid and mineral metabolism and vascular function in 80 heterozygous carriers, 80 GS patients and 80 controls persons (without mutations in SLC12A3 gene).

Study Timeline

• Study Start: 2013-12
• Study First Submitted: 2013-12-18
• Study First Submitted QC: 2014-01-10
• Study First Posted: 2014-01-14
• Primary Completion: 2016-09
• Study Completion: 2016-09
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-13
• Last Update Posted: 2017-01-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Systolic blood pressure evaluated by self-measurement	3 days	self-measurement at home, 3 times a day during 3 consecutive days

Secondary Outcome Measures

Name	Time	Method
Oral glucose tolerance test	1 day
Salt balance	1 day	Blood renin and aldosterone measurements, 24h urinary sodium and aldosterone excretion
Vascular fonction evaluation	1 day	Pulse wave analysis and central blood pressure. Blood and urinary vascular fonction markers
Potassium metabolism	1 day	Dietary intake, blood potassium and 24 h urinary potassium excretion
Glucose and lipide metabolism	1 day	BMI, blood glucose, insulin, cholesterol, LDL, HDL and triglycerides.
Mineral metabolism	1 day	Blood and urinary calcium, magnesium and phosphate. bone remodeling markers
Renal fonction	1 day	Estimated GFR, proteinuria and albuminuria

Trial Locations

Locations (5)

Nephrology Department. Centre Hospitalier Universitaire, Hôpital Dupuytren; 🇫🇷 Limoges, France

Department of Functional Investigations. Hospices Civils de Lyon, Hôpital Edouard Herriot.; 🇫🇷 Lyon, France

Department of Functional Investigations. Assistance Publique Hôpitaux de Paris, Hôpital Tenon; 🇫🇷 Paris, France

Clinical Research Center. Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou.; 🇫🇷 Paris, France

Department of Functional Investigations. Centre Hospitalier Universitaire, Hôpital de Rangueil.; 🇫🇷 Toulouse, France